OBJECTIVE To investigate the effects of Sanren decoction on digestion and absorption function and Akt/NF-κB pathway in rats with Helicobacter pylori(Hp)-associated gastritis(HAG) and spleen and stomach damp heat syndrome. METHODS Seventy-two Wistar rats were randomly divided into blank group(n=12) and modeling group(n=60), and a rat model of HAG with combination of factors[fatigue+diet+bitter cold medicine+environment+biological factors(Hp bacterial solution)] was constructed. After successful modeling, the rats were randomly divided into model group, quadruple therapy group(omeprazole 2 mg·kg−1+amoxicillin 100 mg·kg−1+clarithromycin 50 mg·kg−1+colloidal pectin secret capsule 35 mg·kg−1), Sanren decoction low, medium, high dose groups(3, 7.5, 15 g·kg−1), each group was continuously administered for 21 d. During the experiment, the general conditions of rats were observed; the rapid urease test was performed to detect Hp colonization rate; HE staining was performed to observe the inflammation of gastric mucosa; TUNEL was performed to detect apoptosis in gastric mucosa; the content of Ghrelin, IFN-γ, MTL, GAS, IL-4, IL-10 in serum were detected by ELISA; Western blotting was used to detect the protein expression of caspase-3, Bax, Bcl-2, cAMP, Akt, p-Akt, NF-κB p65, p-NF-κB p65 in gastric mucosa; Real-time PCR was performed to detect Akt, NF-κB p65 mRNA expression in gastric mucosal tissues. RESULTS Compared with the blank group, the mucosal tissue of rats in the model group was significantly damaged, and the Hp colonization rate, apoptosis, protein expression of caspase-3, Bax, p-Akt, p-NF-κB p65 in gastric mucosal tissue, mRNA expression of Akt, NF-κB p65 in gastric mucosal tissue and serum IFN-γ content were significantly increased, while protein expression of Bcl-2 in gastric mucosal tissue and serum Ghrelin, MTL, GAS, IL-4 and IL-10 levels were significantly decreased(P<0.01). Compared with the model group, the mucosal tissue injury of rats in Sanren decoction high dose group was significantly improved, the Hp colonization rate, apoptosis, protein expression of caspase-3, Bax, p-Akt, p-NF-κB p65 in gastric mucosal tissues, mRNA expression of Akt and NF-κB p65 in gastric mucosal tissues and serum IFN-γ content were significantly reduced, while the protein expression of Bcl-2 in gastric mucosal tissues and serum levels of Ghrelin, MTL, GAS, IL-4 and IL-10 were significantly increased(P<0.05). CONCLUSION Sanren decoction can improve the symptoms, inhibit the inflammatory response and functional dyspepsia in rats with HAG spleen and stomach damp heat syndrome, and the mechanism of action maybe related to the regulation of Akt/NF-κB pathway.