Dressing wounds accelerates the re-epithelialization process and changes the inflammatory environment towards healing. In the current study, a lignocellulose sponge containing pentoxifylline (PTX)-loaded lecithin/chitosan nanoparticles (LCNs) was developed to enhance the wound healing rate. Lecithin/chitosan nanoparticles were obtained by the solvent-injection method and characterized in terms of morphology, particle size distribution, and zeta potential. The lignocellulose hydrogels were functionalized through oxidation/amination and freeze-dried to obtain sponges. The prepared sponge was then loaded with LCNs/PTX to control drug release. The nanoparticle containing sponges were characterized using FTIR and SEM analysis. The drug release study from both nanoparticles and sponges was performed in PBS at 37 °C at different time points. The results demonstrated that PTX has sustained release from lignocellulose hydrogels. The wound healing was examined using a standard rat model. The results exhibited that PTX loaded hydrogels could achieve significantly accelerated and enhanced healing compared to the drug free hydrogels and the normal saline treatment. Histological examination of the healed skin confirmed the visual observations. Overall speaking, the in vivo assessment of the developed sponge asserts its suitability as wound dressing for treatment of chronic skin wounds.