Objective: To evaluate the methanolic extracts of aerial parts of Hypericum scabroides (HSM) (200 mg/kg, p.o.) for in vivo anti-inflammatory activity. Methods: The anti-inflammatory activity of HSM was tested in mice weighting (25±5) g. Either vehicle (control group), the methanolic extracts (200 mg/kg) or diclofenac (50 mg/kg), was administered (p.o.) for 60 min before an edema was induced in the mice paw by subcutaneous injection of carrageenin. The mouse-paw volume was measured 1 h, 3h and 6 h after injection of carrageenin. Results: The HSM showed significant reduction of edema in carrageenan induced mice paw edema model at 1 h and 3 h for (78.03±15.54)% and (40.44±16.36)%, respectively. The diclofenac 50 mg/kg exhibited % reduction in paw volume (31.00±11.52)%, (0.80±0.09)% and (9.39±1.99)% after 1 h, 3 h and 6 h, respectively compared to control group. The obtained results revealed that HSM has significant anti inflammatory activity. Furethermore, the chemical composition of HSM was analyzed by using high performance liquid chromatography-diode array dedector. The plant contained pseudohypericin (trace) hypericin (trace), chlorogenic acid (0.0140±0.0005)%, rutin (0.0050±0.0006)%, hyperoside (0.016±0.005)%, isoquercitrin (0.0340±0.0005)% and kaempferol (trace). Conclusions: The obtained results of the present investigation revealed that methanol extract of Hypericum scarbroides has significant anti-inflammatory activity.