BACKGROUND:Poststroke depression is one of the most common psychological behavior disorders after stroke and its mechanism remains unclear. Studies have suggested that microRNAs (miRNAs) involved in neurogenesis and synaptogenesis may play an important role in psychology diseases. OBJECTIVE:To observe the expression of miR-137 in the blood and brain of poststroke depression rats and its effect on the behaviors of rats. METHODS:Thirty-six rats were equal y divided into six groups:control, model, agomir-137, agomir-NC, agomir-137+Grin2A and agomir-137+vector groups. Control group had no treatment. Poststroke depression models were established by ligation of middle cerebral artery and chronic mild stimulation in the latter four groups fol owed by receiving an injection of nothing, agomir-137, agomir-NC, LV-CMV-Grin2A or control plasmids into the left lateral ventricle, respectively. RESULTS AND CONCLUSION:We found significantly lower miR-137 levels in the brain and peripheral blood of post-stroke depression rats compared with normal rats. Vertical scores and horizontal scores on the behavior test were significantly higher in the agomir-137 group than the agomir-NC and model groups at 3 weeks after cerebral ischemia;while, sucrose consumption percentage was also higher in the agomir-137 group at the end of 2 weeks after cerebral ischemia. Luciferase assays showed miR-137 bound to the 3’ UTR of Grin2A, regulating Grin2A expression in a neuronal cel line. Grin2A gene overexpression in the brain of post-stroke depression rats noticeably suppressed the inhibitory effect of miR-137 on post-stroke depression. Overal , these findings show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby exerting an inhibitory effect on post-stroke depression and offering a new therapeutic target for poststroke depression.