Objective: To evaluate the effectiveness of intrathecal injection of methotrexate (MTX) and dexamethasone (DXM) combined with glucocorticoid in treatment for neuropsychiatric systemic lupus erythematosus(NPSLE). Methods: The clinical literatures about intrathecal injection of MTX and DXM combined with glucocorticoid in treatment of NPSLE were collected from January 1996 to December 2016. Meta-analysis was performed by comparing control with treatment group. The control group was treated with glucocorticoid or glucocorticoid combined with cyclophosphamide. The treatment group was treated with intrathecal injection of MTX and DXM combined with glucocorticoid. Results: A total of 6 clinical trials with 256 NPSLE patients were included. There were 126 patients in the control group and 130 patients in the treatment group. Meta-analysis indicated that the treatment group was superior to control group in cerebrospinal fluid pressure, cerebrospinal fluid protein, erythrocyte sedimentation rate, and systemic lupus erythematosus disease activity index (SLEDAI) (all P<0.01). Conclusion: The curative effect of treatment group is superior to that of the control group. However, due to the low methodological quality of the literature, it still needs large sample, multi-center, high-quality clinical research trails.