AIM: To study the protection of compound Hippoph ae rhamnoides L-granule (CHRG) on ischemic injury induced by glutamic aci d (Glu) in the cortical neurons of rat cultured in vitro and its relevant mechanism. METHODS: The cortical neurons of the newbor n rats ( 1 d ) were cultured and separated. The protective effects of CHRG on ischemic injury induced by Glu were observed. The survival rate of the neurons w as measured by MTT method, the content of LDH in extra-cellular bathing media w as measured by colorimetry as well as the content of MDA, the activity of SOD an d GSH-Px in the homogenate of cortical cells. RESULTS: When cel ls were treated with Glu, the content of LDH and MDA increased and the activity of SOD and GSH-Px decreased significantly. The observed group treated with CHRG could effectively prevent these changes. CONCLUSION: The serum preparation of CHRG shows protective effects on the cortical neurons injury indu ced by Glu and the mechanism may be related to suppressing the generation of lip ids peroxides and cleaning excessive free radicals.