Objective To investigate the effects of decoction, ethanol extract, and formulated granules of different processed products of Polygonum multiflorum in conventional doses on kidney injury, renal cell apoptosis and expression of related protein in SD rats. Methods Half male and half female SD rats were randomly divided into 7 groups according to their body weight: normal control group, traditional water extract of raw Polygonum multiflorum group (SW group), traditional water extract of prepared Polygonum multiflorum group (ZW group), 70% alcohol extract of raw Polygonum multiflorum group (SA group), 70% alcohol extract of prepared Polygonum multiflorum group (ZA group), raw Polygonum multiflorum granules without water decocting extraction group ( SK group) and prepared Polygonum multiflorum granules without water decocting extraction group (ZK group). Among them, the rats in the normal group were intragastrically given distilled water, and the other groups were treated with the corresponding drug liquids [6 g/ (kg·d) of crude drug] for consecutive 30 days. At the end of the experiment, changes in the levels of blood urea nitrogen (BUN), creatinine (Crea), uric acid (UA) and β2 -microglobulin (β2 -MG) were measured by a semiautomatic biochemical analyzer. In addition, the histopathological changes of kidney tissues were examined, renal cell apoptosis was detected by TUNEL assay, and the expression of Bcl-2 and BAX was determined by immunohistochemical analysis. Results Compared with the normal control group, the levels of BUN in each drug administration group were significantly lower ( P <0.05, P < 0.01). The levels of Crea, UA, and β2 -MG in each drug administration group all showed an increasing tendency compared with the normal control group, especially, the level of β2 -MG in the ZA group was significantly increased ( P < 0.05). The result of TUNEL assay showed that the average optical density in each drug administration group was significantly higher than that in the normal control group ( P < 0.01). In addition, the expression level of BAX in the SA group was significantly increased ( P < 0.01), but expression of Bcl-2 showed no significant difference among the groups ( P > 0.05). Conclusions Our findings indicate that the long-term administration of Polygonum multiflorum with a daily dose of 6 g/ kg of crude drug can cause some damages to the kidneys, and the degrees of kidney injuries are ranked as alcohol extract > formulated granules > water extract. We would suggest that for patients with impaired renal fuction, Polygonum multiflorum should be used with caution, and do not used for patients with severely impaired renal function. For people long-term using Polygonum multiflorum for health care purposes, it is recommended only to use its water extract, and to control renal function, especially, β2 -microglobulin, at regular intervals, to avoid irreversible kidney injury.