Objective: To evaluate the chondroprotective effect of piroxicam in post-traumatic osteoarthritis model of rat. Study Design: Laboratory based experimental study. Place and Duration of Study: Pharmacology department, Army Medical College, Rawalpindi, from Apr to Jun 2019. Methodology: Project included sixteen rats of Sprague Dawley breed. Osteoarthritis was induced in anesthetized rats by surgical removal of medial meniscus and anterior cruciate ligament resection. After that rats were randomly allocated in two groups with eight rats in each group. Rats of group I were positive control that received 0.2 ml saline intra articularly once weekly for four weeks. Meanwhile rats of group II (treatment group) received 50 µl piroxicam intra articularly once weekly for four weeks. One week after the drug intervention, radiograph of the right knee joint of all rats were taken. Animals were then sacrificed with inhaled chloroform and part of proximal tibia was obtained for histopathological analysis. Results: Comparison of radiographs of both groups depicted a significant p-value of <0.01. Meanwhile mean histopathological score of control group and treatment group were 11.50 ± 1.195 and 6.50 ± 1.195 respectively with a p-value of <0.01. Conclusion: Intra articular administration of piroxicam in post-traumatic Osteoarthritis model of rats resulted in improvement in radiographic grades and histopathology scores.