Objective Investigating the potential anti-inflammatory and analgesic effects of transdermally administered BaGui Zhitong San, and exploring whether its mechanism of action is associated with modulating the COX-2/PGE2 signaling pathway. Methods The effect of BaGui Zhitong San on inflammatory pain was observed through the acetic acid-induced writhing test in mice and the xylene-induced ear edema test in mice. The grouping for both experiments was as follows: 40 SPF-grade male mice were randomly divided into a blank control group, a positive control group(diclofenac diethylamine emulsion 4.02 g/kg), and BaGui Zhitong San groups (1.005, 2.01 and 4.02 g/kg), with 8 mice in each group. The drugs were administered via abdominal topical application for 3 days. There are forty SPF male mice were randomly divided into blank control group, model group, and Bagui Zhitong San(1.005, 2.01 and 4.02 g/kg) group, 8 mice in each group, and after 3 days of external application of the drug to the abdomen, constructed model of left hindfoot swelling in mice given carrageenan gum (except blank control group), determination of interleukin-6(IL-6), determination of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in the blank control group and foot swelling group by Enzyme-Linked Immunosorbnent Assay(ELISA). The expression levels of cyclo-oxygen-ase 1(COX-1), COX-2 and PGE2 were determined by quantitative real-time PCR (q-PCR). Results Bagui Zhitong San (4.02 g/kg) effectively reduced the number of twisting of mouse body caused by glacial acetic acid(P＜0.05), and inhibited the degree of swelling of mouse ears caused by xylene (P＜0.05). The levels of IL-6 and TNF-α in the swollen foot tissues of mice induced by carrageenan (2.01 and 4.02 g/kg) were reduced (P＜0.05), and the levels of IL-1β in the foot tissues of mice induced by carrageenan were reduced(P＜0.05); the levels of COX-1, COX-2 and PGE2 in the group of 1.005, 2.01, and 4.02 g/kg were reduced in the group of 1.005, 2.01, and 4.02 g/kg, compared with that in the group of model mice, COX-1， COX-2 and PGE2 expression levels were reduced, but there was no significant difference in the comparison between groups. Conclusion Bagui Zhitong San can effectively exert anti-inflammatory and anti-nociceptive effects, reduce the expression levels of IL-6, IL-1β, TNF-α and so on, the mechanism of action may be related to the regulation of the COX-2/PGE2 signaling pathway.