Abstract： Objective： To observe the clinical effect of Modified Diankuang Mengxing Decoction combined with western medicine on patients with treatment-resistant schizophrenia (TRS). Methods： A total of 108 cases of patients with TRS were divided into the treatment group and the control group according to the random number table method，with 54 cases in each group. The control group was treated with Aripiprazole and Risperidone， and the treatment group was additionally treated with Modified Diankuang Mengxing Decoction based on the treatment of the control group. After two months of treatment， Positive and Negative Symptom Scale (PANSS) scores， brain injury markers [serum brainderived neurotrophic factor (BDNF)， neuron-specific enolase (NSE)， calcium-binding protein (S100β)] levels before and after treatment as well as clinical effects and incidence of adverse drug reactions were compared between the two groups. Results：The total effective rate was 94.44% in the treatment group， higher than that of 81.48% in the control group， the difference being significant (P＜0.05). Before treatment， there was no significant difference being found in the comparison of negative symptoms， positive symptoms，general psychopathological scores and total scores between the two groups (P＞0.05). After treatment，the scores of all dimensions of PANSS scale and the total scores in the two groups were decreased when compared with those before treatment (P＜0.05)，and the scores in the treatment group were lower than those in the control group (P＜0.05). Before treatment，there was no significant difference in the comparison of the levels of BDNF，NSE and S100β in serum between the two groups (P＞0.05). After treatment， the levels of BDNF in the two groups were increased when compared with those before treatment (P＜0.05)，and the levels of NSE and S100β were decreased when compared with those before treatment (P＜0.05)；BDNF level in the treatment group was higher than that in the control group (P＜0.05)， and the levels of NSE and S100β in the treatment group were lower than those in the control group (P＜ 0.05). The incidence of adverse reactions was 7.40% in the treatment group，lower than that of 22.22% in the control group， the difference being significant (P＜0.05). Conclusion： Modified Diankuang Mengxing Decoction combined with western medicine for TRS patients can improve the clinical effect， alleviate clinical symptoms， regulate the expression levels of brain injury markers， and reduce adverse drug reactions.