Objective To investigate the mechanism of Chaishao Liujun decoction on gastric mucosal cell proliferation and apoptosis in rats with chronic atrophic gastritis (CAG) of liver depression and spleen deficiency. Methods Twenty-six Sprague Dawley rats (male= 13) were randomly divided into normal (n= 6) and model groups (n= 20). CAG rat models of liver depression and spleen deficiency were established and evaluated by the compound factor modeling method. After modeling, they were randomly divided into CAG, vitamin (VI group), and Chaishao Liujun decoction (CS group) groups, with six rats in each group. The normal group was not treated. During the intervention process, the CS group was administered Chaishao Liujun decoction 5. 1 g / ( kg·d), the VI group was given vitamin suspension 240 mg / (kg·d), and the normal and CAG groups were given sterilized drinking water for 4 weeks. HE staining was used to observe pathological changes in the gastric mucosa. Quantitative real-time PCR was used to detect the expression of apoptosis genes c-myc and p53 and Immunohistochemistry was performed to detect PCNA and Ag-NOR. TdT-mediated dUTP nick end labeling staining was undertaken to detect the apoptosis index of the gastric mucosa. Results Compared with the normal group, the activity of the rats in the CAG group was decreased, and the pathological changes showed atrophy of the inherent glands in the gastric mucosa, infiltration of inflammatory cells, and increased expression of c-myc, p53, PCNA, Ag-NOR and the apoptosis index in the gastric mucosa (P< 0. 05 or P< 0. 01). Compared with the CAG group, the activity of rats increased, the pathological atrophy of gastric mucosa improved to a certain extent, and the infiltration of inflammatory cells decreased in the VI and CS groups. The expression of c-myc, p53, PCNA, Ag-NOR and the apoptosis index in the gastric mucosa of rats in CS group was decreased (P<0. 05 or P<0. 01), while the expression of c-myc and p53 in the gastric mucosa of rats in the VI group decreased (P< 0. 05 and P< 0. 01, respectively), and the expression of PCNA, Ag-NOR, and the apoptosis index was decreased, with no significant difference ( P> 0. 05 ). Compared with the VI group, the general condition and gastric mucosa morphology of the CS group were more significantly improved, c-myc and p53 mRNA expression was increased in the gastric mucosal, and the expression of PCNA and Ag- NOR and the apoptosis index were decreased, but the differences were not statistically significant (P>0. 05). Conclusions The proliferation and apoptosis of gastric mucosal cells are closely related to the development and evolution of CAG. Chaishao Liujun decoction has good therapeutic and repair effects on CAG rats with liver depression and spleen deficiency. The mechanism of action may be related to the inhibition of c-myc, p53, PCNA and Ag-NOR expression, regulating the excessive proliferation and apoptosis of gastric mucosal cells.