OBJECTIVE: To evaluate the effects of moxibustion and acupuncture of Zusanli(ST 36) and Zhongwan(CV 12) acupoints on chronic atrophic gastritis(CAG) in rats, and to study the mechanisms behind their actions.METHODS: Forty-four male Sprague-Dawley rats were induced with CAG by intragastric administration of 40% ethanol combined with free drinking of N-methyl-N′-nitro-N-nitrosoguanidine and irregular feeding for 12 weeks, followed by daily treatment with moxibustion or acupuncture for 2 weeks. Histopathologic examination, Western blotting of cytokines [epidermal growth factor(EGF),EGF receptor(EGFR), extracellular signal-regulated kinase(ERK), phosphorylated ERK(p-ERK)], and1 H NMR-based metabolic profiling of gastric tissues were used to measure changes related to CAG modeling and treatment.RESULTS: Moxibustion and acupuncture at Zusanli(ST 36) and Zhongwan(CV 12) each relieved CAG-induced abnormalities in histopathology and cytokine expression of ERK and p-ERK. Only moxibustion treatment regulated the expression of EGF and EGFR. Metabolites that were increased in gastric tissue by CAG induction(alanine, nicotinamide adenine dinucleotide phosphate, uracil DNA glycosylase, lactate, glycerol and adenosine) were restored to normal levels after moxibustion treatment; acupuncture treatment only normalized the levels of adenosine monophosphate and glycerol.CONCLUSION: Our findings suggest that moxibustion or acupuncture at Zusanli(ST 36) and Zhongwan(CV 12) can significantly improve the condition of CAG in rats. These treatments exert their effects on CAG through different mechanisms.