Background Chronic low-grade inflammation is a feature of chronic kidney disease associated with increased risk of multiple morbidities and mortalities. Dialysis patients lead a sedentary life style which could add to this risk. Aim assessment of the effect of intradialytic exercise IDE on inflammatory markers in prevalent hemodialysis HD patients. Patients and Methods This longitudinal prospective study included 40 adult patients on regular HD, divided equally into 2 groups; Exercise Group (n = 20); received IDE 3 times/week for 3 months and Non-exercise Group (n = 20) matched in age and sex acting as controls. Patients were subjected to full history taking and clinical examination. Physical performance assessment using Short Physical Performance Battery tests (SPBT), Laboratory investigations included; Complete blood picture, C-reactive protein (CRP) and interleukin 6 (IL6) assessed using Enzyme linked immunosorbent assay. All assessments were repeated 3 months after regular IDE. Results At baseline, there was no difference between both groups regarding physical performance or inflammatory markers. After 3 months, SPBT was significantly increased in Exercise group (P < 0.001). Also, both serum CRP and IL-6 levels showed significant decrease in Exercise group compared to baseline (P < 0.001), while no similar change was noticed in non-exercise group. Conclusion The significant decrease in serum CRP and IL-6 levels after 3 months of regular IDE and the improvement in physical performance in exercise group implements that regular IDE exercise training program can improve physical function and inflammation in hemodialysis patients. Further studies on larger number of patients is warranted.