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Osteoarthritis (OA) is the most common joint disease in both humans and animals, and it results in movement restriction and pain at the affected area. This disorder affects more than 25% of people over 60 years of age, and it is considered universal for 70-year-old people. OA is estimated to affect over 20% of the canine population from the United States of America. The present study aimed to evaluate the treatment of rats that were surgically induced to OA using two different drug therapies, one with pentosan polysulfate, one with betamethasone, and one with chondroitin sulfate/ glucosamine. In order to produce joint disease, the cranial cruciate ligament was surgically transected. Animals were kept and treated for eight days after surgery and were assessed via both radiographies and tomographies taken before surgery and eight weeks later. All animals were euthanized having both macroscopic and microscopic analysis performed to evaluate the disorder progression and therapeutic action. Macroscopic analysis showed lesion in the knees subjected to OA induction. The untreated animals presented major lesions whereas the treated ones presented mild to moderate lesions. In conclusion, pentosan polysulfate is recommendable for the treatment of iatrogenic joint lesions in rats since the other treatments showed no significant difference.