Accurate verification of the time passed since death is a challenging task in daily forensic investigations, chiefly in homicidal or unwitnessed death. The study evaluated the applicability of the time-dependent changes in histological structure, DNA content,and oxidant/antioxidant parameters in rat’s skeletal muscles in an attempt to reach a reliable method for post-mortem interval (PMI) estimation. We used 56 adult male albino rats. These animals were sacrificed then and allocated randomly to seven groups (eight rats each). First group: rats were dissected to obtain samples from quadriceps femoris muscles promptly after death. While the rats in the second, third, fourth, fifth, sixth and seventh groups were dissected to get muscle samples from quadriceps femoris at 6, 24, 48, 72, 96 and 144 hours postmortem (hpm). The results showed that a significant gradual histopathological alteration of muscle structure started at 48 hpm and progressed afterwards. Also, the DNA degradation percentage increased significantly parallel to the increased oxidant parameter levels from 6 to 144 hpm. Our results concluded that changes in oxidant/antioxidant parameters and DNA degradation, as well as the histological examination of muscle tissues, showed a strong correlation with post-mortem intervals. Consequently, the integration of all these parameters can provide a valuable method of post-mortem intervals estimation. KEYWORDS Time since death; DNA degradation; single cell gel electrophoresis; oxidants; muscle; post-mortem changes