ABSTRACT The present study was designed to investigate the effect of FPZ, a total flavonoids ointment topical application from Pouzolzia zeylanica var. microphylla (Wedd.) Masam, Urticaceae, on skin infections in mice. FPZ ointment anti-infective effect was investigated on Staphylococcus aureus-induced skin abscess and skin ulcers in mice by evaluating the variation in abscess volume, histopathology of skin tissue and healing rate. Secondary, it is topical anti-inflammatory activities on carrageenan-induced hind paw edema in mice was estimated. Besides, FPZ ointment fingerprint was performed by using ultra-performance liquid chromatography and FPZ ointment chemical constituents were isolated and identified by repeated column chromatograph and spectroscopic methods. The results revealed that FPZ ointment topical application at the concentration of 2.5–10% could attenuate skin abscess and ulcers and accelerate wound healing, as compared with control group treated with vehicle (p < 0.05). The histological analysis indicated that FPZ ointment acted via inflammation inhibition, granulation promotion and epidermis formation. Moreover, FPZ ointment effectively inhibited carrageenan-induced paw edema in a dose-dependent manner, especially 10% FPZ which showed superior activities in comparison with dexamethasone used as reference drug. FPZ ointment topical application showed a significant anti-infective effect against pyogenic bacterial skin infection in mice.