BACKGROUND: Post-stroke depression (PSD) has a significant effect on patients' quality of life and is often accompanied by a decrease in serum brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) levels. Although exercise is an effective way to improve the body's endocrine environment, traditional high-intensity resistance exercise is not yet readily accepted. PURPOSE: To compare the acute effects of high and low resistance training with or without blood flow restriction on perception, BDNF, and VEGF levels in patients with PSD. METHOD: A total of 24 patients with PSD participated in 2 40% 1- Repetition Maximum (RM) low-intensity resistance training sessions (the low-intensity resistance training group (LOW group) had no blood flow restriction belt; the low-intensity blood flow restriction group (L-BFR group) was required to wear a 120-160 mmHg pressure cuff at the proximal end of the limb) and 1 80% 1-RM high-intensity resistance training session (HIGH group). Elbow venous blood was collected before and after exercise to test for ratings of perceived exertion (RPE), serum blood lactic acid (BLA), BDNF, and VEGF levels. RESULT AND CONCLUSION: There were no statistical differences between the RPE, BLA, BDNF, and VEGF levels of each group before exercise. After exercise, the RPE, BLA, and BDNF levels of the LOW group increased significantly (P < 0.05); the change in VEGF level of the LOW group was not significantly different from that before exercise (P > 0.05), and the indexes of the L-BFR group and the HIGH group were significant after the increase in exercise (P < 0.05). Analysis between groups showed that the changes in BLA, BDNF, and VEGF levels in the L-BFR group and HIGH group were higher than those in the LOW group, and the statistical difference was significant (P < 0.05); there was no change between the statistical difference of the L-BFR group and HIGH group (P > 0.05). The difference in RPE before and after exercise in the HIGH group was significantly higher than that in the L-BFR group (P < 0.05) and the difference in RPE before and after exercise in the L-BFR group was significantly higher than that in the LOW group (P < 0.05). Blood flow restriction resistance exercise may increase the serum BNDF and VEGF levels of PSD patients by increasing the body's BLA concentration. Although its effect is similar to that of traditional high-intensity resistance exercise, subjective physical strength is lower during blood flow restriction resistance exercise.