OBJECTIVE To investigate the protective effects of musk extract (ME) and its possible mechanism on rat's cerebral cortical neurons with inflammatory injury induced by lipopolysaccharide (LPS). METHODS Neurons and astrocytes from newborn rat cerebral cortex were cultured in vitro respectively, and the astrocyte conditioned medium (ACM), obtained by treating astrocytes with 10 mg/L LPS and different concentrations of ME for 24 h, was added in the culture fluid of neurons. The survival rate and apoptotic rate of neurons were measured by MTT method and AO/EB stain; and the changes of inflammatory factors in the ACM were determined by ELISA. RESULTS The survival rate (%) of neurons treated by ACM with ME in concentrations of 18 mg/L, 36 mg/L, 72 mg/L and 144 mg/L was 52.55 +/- 3.52, 55.77 +/- 2.36, 64.89 +/- 3.45 and 73.67 +/- 1.80, respectively, significantly higher than that in the model neurons (43.62 +/- 4. 51, P < 0.05), while the apoptotic rate (%) in them, 68.11 +/- 2.16, 44.27 +/- 3.68, 32.56 +/- 2.14 and 21.89 +/- 2.46, respectively, was significantly lower than that in model neurons (71.33 +/- 3.25, P < 0.05 or P < 0.01). Level of IL-6 was decreasing along with the raising of ME concentration in the ACM, showing a concentration-dependent state. CONCLUSIONS ME shows apparent protective effect on neurons against inflammatory injury, especially in a high concentration (144 mg/L), which may be associated with the reduction of IL-6 secreted by astrocytes.