Abstract：Objective： A rat model of primary hepatocellular carcinoma (HCC) was established using three different doses to establish an efficient, stable, and economical animal model of HCC. Methods： Forty-five male SD rats were randomly divided into four groups, namely the normal group, the diethylnitrosamine (DEN) 50 mg/kg dose group (low dose group), the 70 mg/kg dose group (medium dose group), the 200 mg/kg dose group (high dose group), 6 in the normal group and 13 in each of the remaining groups. The normal control group received no treatment. In the model group, the low dose group was injected intraperitoneally twice a week during weeks 1-4 and once a week during weeks 5-12; the intermediate dose group was injected intraperitoneally once a week for 16 consecutive weeks; and the high dose group was administered once in a single dose and the rats in each group were followed up to 16 weeks. The establishment of the model and optimal evaluation were verified by survival rate, pathological tests, biochemical tests, liver and spleen index calculation, immunohistochemistry, ELISA, and other assays. Results： The survival rate was 100% in the normal group, 46.15% in the low-dose group, 69.23% in the medium-dose group, and 84.61% in the high-dose group. The liver tissues of the rats in the normal group showed no abnormality to the naked eye; the liver of the rats in the low-dose group became darker in color, rougher in surface, with a small number of cancerous nodules and slightly hard texture; the liver of the rats in the medium-dose group was rough in surface, with several small cancerous nodules and scattered massive occupying nodules and hard texture; The liver of rats in the high-dose group became lighter in color, slightly rougher in surface, with no obvious cancerous nodules; HE staining showed that the liver tissues of rats in the low- and mid-dose groups were structurally disorganized, with large cellular heterogeneity and tumor cells. HE staining showed that the liver tissues of rats in the low and intermediate dose groups were structurally disorganized, with large cellular heterogeneity and tumor cell formation, while the structure of the liver lobules of the high dose group was unclear, with different degrees of edema, degeneration and necrosis of liver cells, and no obvious tumor cell formation was seen. Compared with the normal group, serum liver function (alanine aminotransferase, ALT), (aspartate aminotransferase, AST), (and total bilirubin, TBIL) were elevated in the low, medium, and high dose groups, and ALT and AST were significantly elevated in the low dose group, P＜0.05, the difference was statistically significant. The difference was statistically significant, ALT, AST and TBIL were significantly elevated in the middle dose group, P＜0.05, the difference was statistically significant, and the difference was not statistically significant in the high dose group, although it was elevated, P＞0.05; compared with the normal group, the serum (International Standardised Ratio, INR) level of the low dose group was significantly elevated, P < 0. 05, the difference was statistically significant; serum APTT (activated partial thromboplastin time, APTT), PT (prothrombin time, PT), AFP (alpha-fetoprotein, AFP ) were increased, P > 0.05, the difference was not statistically significant; serum APTT, PT, INR and AFP levels were significantly increased in the mid-dose group, P < 0. 05, the difference was statistically significant; serum PT and AFP levels were increased in the high-dose group, P < 0.05, the difference was statistically significant, and serum APTT levels were slightly increased, P > 0.05, the difference was not statistically significant; liver and spleen indexes were increased in the middle-dose group, P＜0. 05, the spleen index increased in the low dose group, P＜0.05, and the liver index increased in the high dose group, P＜0.05, the difference was statistically significant; the optical density value of liver tissue (alpha-fetoprotein, AFP) increased significantly in the low, medium and high dose groups, P＜0.05, the difference was statistically significant. Conclusions： Both the low and mid-dose groups could successfully induce the HCC rat model, but the pathological changes and biochemical findings of the mid-dose group were more in line with the pathogenesis of human HCC, and with fewer administrations and higher survival rate of the rats, it was possible to establish a more cost-effective and superior HCC model.