Objective To observe the effect of risperidone on serum brain derived neurotrophic factor ( BDNF) in first-episode schizophrenic patients. Methods In the treatment group, 90 first-episode schizophrenics were treated with risperidone for 16 weeks, and the dose of risperidone was (3.79±0.88) mg·d-1. Serum BDNF levels were measured before treatment, at 2, 8, and 16 weeks after treatment. The severity of schizophrenia symptoms was assessed by the positive and negative symptom scale ( PANSS) before and after sixteen weeks of treatment. Serum BDNF concentrations were measured in 90 healthy controls. Results BDNF in the control group was (22.867±6.051) ng·mL-1. The serum BDNF levels before treatment and at the end of week 2, 8, 16 after the treatment in the treatment group were (14.256±4.096), (13.078±3.462), (18.001±5.753), (21.089± 6.692) ng·mL-1 , and the serum BDNF level was significantly lower in the treatment group than that in the control group ( P<0.01) . After the treatment, the level of BDNF in the treatment group decreased at first and then increased, compared with that before treatment, the difference was significantly ( P<0.05 or P<0.01) . The level of BDNF in the treatment group at the end of week 16 was not significantly different from that of the control group ( P>0.05) . After treatment, the total score of PANSS scale and its subscales decreased, the difference was significantly (P<0.01). At the end of week 16, the PANSS subscale reduction rate was positively correlated to the serum BDNF concentration change (r=0.499, P=0.001). The change rate of serum BDNF concentration at the end of week 16 was not correlated with the dose of risperidone (r=0.103, P=0.335). Conclusion BDNF is abnormal in the first episode of schizophrenia, which can be improved by risperidone treatment.