In the osteoarthritis pharmacotherapy, there is a high demand to define drugs with a combined effect of cartilage degradation arrest and a high symptomatic relief capacity. In testing of such drugs, the C-telopeptide of collagen type II (CTX-II) is a suitable biomarker. In the current study, we assessed the serum fraction of CTX-II in 36 Wistar rats, 27 of which were injected with mono-iodoacetate in the left knee, in order to induce osteoarthritis, the remaining 9 being treated with intra-articular saline solution (negative controls). After 3 weeks, the 27 iodoacetate-injected rats were treated with placebo (9 animals) and meloxicam (low-dose, 0.2 mg/kg bw and high-dose, 1 mg/kg bw, 9 animals in each group) for a period of 4 weeks. Baseline, 4th week (treatment withdrawal) and 8th (end-point) week CTX-II levels were assessed along with histopathological modifications in each group. With comparable baseline levels in groups II-IV (16.91-20.72 pg/mL), a significant decrease of CTX-II (3.08 pg/mL, p=0.007) has been observed after 4 weeks of treatment in the high-dose meloxicam group, followed by an increase at the end-point to values yet much lower than those detected at baseline. According to these results, meloxicam suppresses efficiently not only the recruitment of inflammatory cells, but also the breakdown of collagen type II, even 4 weeks after the end of the therapy, a fact that should be confirmed in human clinical studies and exploited in therapeutic schemes.