Objectives: Oral pentoxifylline shows modest, non-significant effect on the healing rates of chronic wounds. The present research aimed to formulate topical pentoxifylline-hydroxypropyl methylcellulose (HPMC) gels and evaluate their physico-chemical properties, in vitro release characteristics and in vivo wound healing effects. Methods: Six gel formulations containing pentoxifylline (F1-F6) were prepared using HPMC with varying grades and concentrations. The physicochemical properties of gel formulations were evaluated in term of drug content, spreadability, rheological properties, swelling, and release characteristics. The efficacy of optimized formulation was further evaluated using in vivo excision wound models in rats. Results: The spreadability, flow index and swelling percentage of gel formulations ranged 10.71-12.24 gcm/sec, 0.33-0.91 and 148.61-8011.61%, respectively. The rheological study of the prepared formulations exhibited pseudoplastic behavior, which is a characteristic feature of topical gels. Swelling results of F5 and F6 deduced that the cross-linked structures were formed between the polymeric chains. The in vitro drug release profiles of all formulations were found to be followed Higuchi model. The in vivo evaluation performed using rat excision wound model showed significant difference (P < 0.05) in the percentage reduction of wound size between treatment and control groups. The treatment group exhibited complete healing by day 13 as compared with day 15 in the control group. Conclusions: These findings indicated that F5 gel formulation had demonstrated effective release profile for pentoxifylline. The in vivo results confirmed that F5 has pronounced wound healing effects when employed topically.