Whole-body cryotherapy (WBC) has been frequently used to supplement the rehabilitation of patients with rheumatoid arthritis (RA). The aim of this study was to compare the effect of WBC and traditional rehabilitation (TR) on clinical parameters and systemic levels of IL-6, TNF-α in patients with RA. The study group comprised 25 patients who were subjected to WBC (-110 °C) and 19 patients who underwent a traditional rehabilitation program. Some clinical variables and levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were used to assess the outcomes. After therapy both groups exhibited similar improvement in pain, disease activity, fatigue, time of walking, and the number of steps over a distance of 50 m. Only significantly better results were observed in HAQ in TR group (p < 0.05). However, similar significant reduction in IL-6 and TNF-α level was observed. The results showed positive effects of a 2-week rehabilitation program for patients with RA regardless of the kind of the applied physical procedure.