The mesocortical tract (MCT) and mesolimbic tract (MLT), dopaminergic pathways originating from the ventral tegmental area in the midbrain to the ventral striatum (nucleus accumbens) and prefrontal cortex, play a crucial role in regulating incentive salience. This study aimed to investigate the potential changes in the MCT and MLT pathways following ischemic stroke, such as middle cerebral artery (MCA) infarction. We enrolled thirty-six patients with MCA infarction and forty healthy individuals with no history of psychiatric or neurological disorders. Using diffusion tensor tractography, we examined the injury to the affected and unaffected MCT and MLT pathways in patients with MCA infarction, comparing them to the control group. Our findings revealed a significant difference in the mean values of fractional anisotropy (FA) and tract volume (TV) of the MCT and MLT pathways between the patient and control groups (p< 0.05). Specifically, the mean FA of the MCT and MLT showed a decrease of 7.94% and 6.33%, respectively, in the affected side compared to the control group (p< 0.05). Similarly, the mean TV of the MCT and MLT showed a decrease of 73.22% and 78.79%, respectively, in the affected side compared to the control group (p< 0.05). These changes were significantly different from those of the unaffected MCT, MLT, and control groups (p< 0.05). Our study suggests that MCA infarction can cause significant damage to the affected MCT and MLT pathways, potentially contributing to our understanding of the pathophysiology of post-stroke depression.