To analyze the action of strontium ranelate (SR) and melatonin in isolation or in association in knees, liver and kidneys of rats Wistar with induced osteoarthritis (OA). Methods: Thirty male rats were induced to OA through an anterior cruciate ligament transection (ACLT), and treated with melatonin and SR in isolation or in association. Morphological, histopathological, histochemical and morphometric analysis were realized of the structure of the articular capsule, as well as histopathological analysis of liver and kidneys from the animals. Results: The experimental model was successful. The association of the drugs presented chondroprotective pharmacodynamics. However, more successful results were identified from analysis of animals in which received melatonin in isolation, regarding biochemical parameters of glutamic oxalacetic transaminase. The prepared slide samples of liver and kidneys from groups submitted to the isolated use of SR and melatonin or the association of these drugs presented no differences, when compared to the control group. Discussion: The administration of the drugs presented chondroprotective effect and prevented from the aggravation of articulate damages, and was not capable of modifying the histology of liver or kidneys. This finding suggests a safe association for the treatment of OA, however it requires further investigation in order to expand therapeutic perspectives regarding improvements of the quality of life of individuals in our society.