Background: Peripheral artery occlusion is the final stage of complications in peripheral arterial disease, which has a serious negative impact on the quality of life of patients. A study conducted in Germany found that 66% of the over 40,000 patients diagnosed with peripheral artery occlusion required limb amputation within four years of diagnosis. The primary treatment goals are to improve limb blood flow, alleviate pain, accelerate tissue regeneration, and prevent cardiovascular complications. Recent studies emphasize that microsurgical techniques may accelerate tissue regeneration and improve treatment outcomes. Aim: This study aimed to evaluate and compare the effects of end-to-end (ETE) and end-to-side (ETS) microvascular anastomosis in a rat model of ischemia, focusing on tissue regeneration. Materials and Methods: Thirty Wistar rats were divided into two groups (control group 10 rats, ischemic group 20 rats) at the Bio-Medical Research Institute of the Mongolian National University of Medical Sciences. Ischemia was induced in the experimental group, and ETE and ETS anastomoses were performed using donor arteries, which were preserved for three days. Preoperative and 21-day postoperative body weight, artery size, and blood flow were measured and analyzed to determine the results. Results: In the control group, the average body weight was 227.86±21.11 grams before surgery, which increased by 12.38 grams to 240.24±25.77 grams post-surgery (p<0.01). In the ischemic group, the rats that underwent ETE anastomosis had an average weight of 239.67±26.96 grams before surgery, which decreased to 234.3±27.20 grams immediately after surgery, but increased to 250.67±27.09 grams after 21 days (p<0.05). The ETS group showed an increase from 235.18±22.39 grams to 249.62±21.12 grams after 21 days (p<0.01). The surgical duration for the control group was 24.51±2.29 minutes, while the ischemic group required 39.75±0.89 minutes for ETE and 46.65±8.12 minutes for ETS anastomoses (p=0.001). Intraoperative blood loss in the control group was 0.27±0.12 ml, whereas the ischemic group showed blood loss of 0.58±0.13 ml for ETE and 1.12±0.61 ml for ETS, with some instances reaching 2.35 ml (p<0.01). Conclusions 1. The body weight of the control rats increased to 240.24±25.77 grams after 21 days, while the ischemic group showed an increase to 250.67±27.09 grams, indicating improved tissue regeneration and successful microsurgical anastomosis. 2. Although PCNA and KGF protein expression levels decreased, tissue regeneration was robust, as evidenced by the continued regeneration observed 21 days after the microsurgery, indicating successful microvascular surgery. Differences in the response to ischemic changes were observed across tissues, with increased expression of KGF and PCNA in the skin and muscle tissues, further supporting the effectiveness of the regenerative process.