Objectives: To compare the local effect of therapeutic doses of meloxicam and diclofenac on the muscle of rats at different periods by intramuscular injection. Materials and methods: Thirty six adult albino rats were divided equally into 6 groups. The 1 st and 2 nd groups were injected intramuscularly with normal saline for 2 and 4 weeks respectively, the 3 rd and 4 th groups were injected intramuscularly with meloxicam for 2 and 4 weeks respectively, the last 2 groups were injected intramuscularly with diclofenac sodium also for 2 and 4 weeks respectively. The drugs were injected into the quadriceps femoris muscle of the right femur once each day till the end of the period stated. The specimens were histologically processed, stained with hematoxylin and eosin and examined with light microscope. Results: No changes were seen in quadriceps femoris muscles of groups 1, 2, 3 and 4, whereas group 5 showed congested blood vessels within normal muscle tissue. In Group 6 mononuclear inflammatory cells infiltration, vascular congestion, fibrosis, degenerative changes and muscle tissue necrosis were seen. Conclusion: Meloxicam is safer than diclofenac sodium on muscular tissue after a long-term daily intramuscular injection.