Background: We have previously reported the antineoplastic effects of a cannabinoid agonist in gastric cancer cells. Our aim was to evaluate this in a murine xenograft model. Methods: Animal models were created after injecting AGS gastric cancer cells subcutaneously into the flank of male BALB/c-nude mice. A cannabinoid agonist, WIN 55,212-2 (7 mg/kg body weight) or vehicle was injected around the tumor subcutaneously every 24 h for 14 days. Tumors were explanted for analysis. Results: Tumor volume decreased by 30% in the WIN 55,212-2-treated group compared to the group treated with vehicle (p < 0.05). Apoptotic cells were found more commonly in the WIN 55,212-2 treatment group than in the control on immunohistochemistry. Compared to the control, WIN 55,212-2 treatment significantly increased caspase-3 cleavage and decreased MMP-2, MMP-7 and MMP-9 protein levels significantly (all p < 0.05). VEGF-A protein level was not different between the 2 groups. Conclusion: WIN 55,212-2 has antineoplastic effect on the gastric cancers in in vivo model.