Abstract: Objective To explore the influence of covering of auto-crosslinked sodium hyaluronate gel in combination with xenogenic acellular dermal matrix (ADM) on healing of full-thickness skin defect wound in pig. Methods Totally four 10 cm×10 cm full-thickness skin defect wounds were reproduced symmetrically on both sides of spine on the back of each one of the six Chinese experimental minipigs. After autologous microskin grafting, the 4 wounds in each pig were divided into 4 groups according to the random number table, with 6 wounds in each group. Wounds in allogenic skin group (AS) were covered by full-thickness skin from one (not the recipient) of the 6 pigs; wounds in xenogenic skin group (XS) were covered by full-thickness skin of sheep; wounds in xenogenic ADM group (XA) were covered by ADM of sheep; wounds in combination group (C) were covered by ADM of sheep combined with auto-crosslinked sodium hyaluronate gel. The wounds were bound up with pressure, and the dressing was changed once every 7 days. On post surgery day (PSD) 7, 14, 21, 28, 35, and 42 when changing dressing, the condition of wounds and the exfoliation of the covering on microskin were observed, and the complete exfoliation time of the covering was recorded. On PSD 28, 35, and 42, the wound healing rate was calculated. Data were processed with one-way analysis of variance and SNK test. Results (1) On PSD 7, no fluid appeared under the covering of wounds in groups AS and C, while plenty of fluid appeared under the covering of wounds in groups XS and XA. From PSD 14 to 35, most of the full-thickness skin of pig in group AS did not exfoliate. All the full-thickness skin of sheep in group XS exfoliated, leaving a lot of crusts on the surface of the wounds on PSD 14. Most of the ADM of sheep in group XA separated from the wound with the crusts turning dry and exfoliating on PSD 14. All the ADM of sheep exfoliated with most of the wounds healed in group C on PSD 35. On PSD 42, all the full-thickness skin of pig in group AS exfoliated, leaving most of the wounds unhealed; all the crusts exfoliated and the majority of wounds were healed in group XS and XA group; all the wounds in group C were healed. (2) Compared with that in group C[(32.7±3.3) d], the complete exfoliation time of the covering was obviously shorter in group XS[(15.2±4.8) d]and group XA[(22.2±6.3) d], with P values below 0.05, while the complete exfoliation time of the covering in group AS[(44.8±2.7) d]was obviously longer (P<0.05). (3) On PSD 28, 35, and 42, the wound healing rates in groups XS and XA[(21.2±2.6)%, (51.4±2.4)%, (89.6±2.8)%, and (23.7±3.4)%, (53.6±6.3)%, (91.3±4.9)%, respectively]were obviously lower than those in group C[(35.1±3.4)%, (62.1±6.7)%, (98.8±1.0)%, respectively, with P values below 0.05]. On PSD 42, the wound healing rate in group AS[(44.0±3.8)%]was significantly lower than the rates in the other 3 groups (with P values below 0.05). Conclusions Auto-crosslinked sodium hyaluronate gel combined with ADM of sheep used as covering of microskin grafts on full-thickness wound in pig can lengthen the persistence time of ADM of sheep on the wound, as well as promote wound healing.