BACKGROUND AND THE PURPOSE OF THE STUDY: It has been shown that nigella sativa L. and Portulaca oleracea L. have many antioxidant components. In the present study, the cytoprotective effect of ethanolic and aqueous extracts of N.sativa and P.oleracea against hemolytic damages induced by free radical initiator, AAPH [2, 2' azobis (2- amidinopropane) hydrochloride] was evaluated.METHODS: Hemolysis was induced by addition of AAPH. To study the cytoprotective effect, aqueous (50, 200, 300, 400, 800 ?g/ml) and ethanolic (25, 100, 150, 200 and 400 ?g/ml) extracts of N. sativa and aqueous (25, 50, 100, 150, 200 and 400 ?g/ml) and ethanolic (300, 600, 900, 1200 and 1800 ?g/ml) extracts of P. oleracea were employed. RBCs were incubated with both extracts and AAPH at 37 ?C for 6 hrs. In order to evaluate the impact of the time of addition, extracts were added one and 2 hrs after AAPH. Samples of suspensions were removed at different times and the degree of hemolysis was assessed spectrophotometrically by reading the absorption of supernatants at 540 nm. RESULTS: Aqueous (300, 400 and 800 ?g/ml) and ethanolic (150, 200 and 400 ?g/ml) extracts of N.sativa and also, aqueous (100, 150, 200 and 400 ?g/ml) and ethanolic (1200, 1800 ?g/ml) extracts of P.oleracea showed concentration-dependent cytoprotective effects. Addition of extracts one hour after AAPH reduced but did not eliminate protective activities of extracts. CONCLUSION: Cytorotective effect of aqueous and ethanolic extracts of N. sativa and P. oleracea against AAPH- induced hemolysis may be related to antioxidant properties of these plants.