Chronic kidney disease (CKD) is associated with a complex state of immune dysfunction characterised by immune depression, which predisposes CKD patients to infections, and by immune activation resulting in inflammation, which is associated with cardiovascular disease among these patients. It has been suggested that regular moderate exercise may enhance immune function and exert anti-inflammatory effects. However, such effects are still unclear in CKD. Therefore, we investigated the effects of acute and regular (1-month and 6-months) moderate intensity aerobic exercise (walking) on measures of immunity and inflammation in pre-dialysis CKD patients. A single bout of walking exercise induced an overall immune and inflammatory response that was comparable to that observed in healthy individuals, with no indication of harmful effects to patients underlying state of immune dysfunction. Acute exercise induced a normal pattern of mobilisation of immune cells. Concerning immune cell function, acute exercise had no effect on T lymphocyte and monocyte activation, while it actually improved neutrophil responsiveness to a bacterial challenge in the recovery period. In addition, acute exercise induced a systemic anti-inflammatory environment, evidenced by the marked elevation in plasma IL-10 levels after exercise, which was most likely mediated by the observed increase in plasma IL-6 levels. Regular walking exercise exerted anti-inflammatory effects, with no apparent detrimental effects to patients immune and inflammatory status. Regular exercise led to improvements in the systemic inflammatory status (ratio of pro-inflammatory IL-6 to anti-inflammatory IL-10 cytokine levels) that were accompanied, and most likely mediated, by the observed down-regulation of T lymphocyte (only evident at 6-months) and monocyte activation. In addition, a reduction in IL-6 production in PBMC and whole blood cultures was also observed (only assessed at 1-month). Regular exercise had no effect on circulating immune cell numbers and neutrophil degranulation responses. These findings provide compelling evidence that walking exercise is safe from an immune and inflammatory perspective and has the potential to be an effective anti- inflammatory therapy in pre-dialysis CKD patients.