Objective To investigate the effects of safflor yellow (SY) injection on acute lung injury (ALI) rats induced by oleic acid (OA) and its potential mechanism. Methods Wistar rats were randomly divided into six groups,including control group,OA group,OA+10 mg/kg anisodamine group,OA+8 mg/kg SY group,OA+16 mg/kg SY group,and OA+32 mg/kg SY group. Normal saline or anisodamine or SY were pretreated before 0.18 g/kg OA iv injection. The arterial partial pressure of oxygen,the pulmonary water content index,and MPO activity in lung tissue were determined; The mRNA level of TNF-?,IL-1?,IL-6,ICAM-1,and VCAM-1 were measured by RT-PCR; And NF-?B p65 protein in nucleus observed by immunohistochemical technology,while the level of p38 MAPK protein phosphorylation in lung tissue was analyzed by Western blotting. Results The arterial partial pressure of oxygen in all SY groups was higher than that in OA group,while the pulmonary water content index and MPO activity were lower than those in OA group,as well as the mRNA level of the above inflammatory cytokines and the NF-?B p65 in nucleus and level of p38 MAPK phosphorylation. Conclusion SY could alleviate the lung tissue edema,increase the arterial partial pressure of oxygen,and depress MPO activity in ALI rat induced by OA. The SY mechanism of attenuating the acute lung injury may be associated with inhibiting the p38 phosphorylation and NF-?B activation and reducing inflammatory factors expression.