Objective Study the effect of NMDA receptor antagonist GAPA on the [Ca 2+ ]i of the bilirubin precipitated brain tissue. Methods 10 ug/g of GAPA was administrated peritoneally to Gunn rat with bilirubin induced encephalopathy, brain tissue suspensions was prepared, Fura 2/AM was loaded. the neural cytosolic Ca 2+ was measured by flurescence imaging analysis. Results The concentration of neural cytosolic Ca 2+ in bilirubin precipitated brain tissue was significantly more than that in the control group; NMDA receptor antagonist GAPA could significantly decrease the cytosolic Ca 2+ overload. Conclusion Cytosolic Ca 2+ overload was found in the bilirubin precipitated brain tissue. NMDA receptor antagonist GAPA could prevent the cytosolic Ca 2+ overload in bilirubin induced brain tissue.