Background: Regarding postmortem estimation, the evaluation of early histological and miRNA molecular changes have been of great concerns among forensic scientists due to uncertainty of known conventional methods. The histological and miRNA molecular changes in incisional wound remain poorly described. Purpose: This evaluation presents a histo-molecular approach that could be used to estimate the early post mortem interval in incisional wound. Methods: The histological and miRNA (205 and 21) changes were evaluated in 18 female albino rats with incisional wound at three interval times: 0, 24, and 48 h after infliction. Results: The wound margin showed progressive morphological changes with increasing postmortem interval. Inflammatory phase had appeared immediately after infliction. After this period, degenerative changes began. mRNA-205 and 21 expressions, detected via real-time PCR, were increased significantly to reach their higher levels at 24 h after wound infliction, then they were significantly diminished with increasing postmortem interval. Conclusions: Our results suggest that histological and miRNA-205 and miRNA-21 changes, occurred at perimortal incisional wound, could be helpful in forensic work regarding postmortem estimation.