OBJECTIVETo explore the mechanism of recombinant thymosin beta4 (Tbeta4) accelerating skin wound healing in rats by regulating laminin 5 expression.METHODSTwo full thickness 8 mm punch wounds were made at the costovertebral angle on dorsal surface of each adult male rats weighing 200-250 g. Sixty rats were randomized into the control group (n = 15) and the experimental group (n = 45), which was subdivided into low, medium and high dose groups (n = 15). Tbeta4 was applied topically at 2, 6, 18 microg in 50 microL PBS for every 12 hours after model making in the experimental group. The identical amounts of phosphate buffered saline was applied in the control group. Wound healing was observed after model making and immunohistochemical observation was conducted 2, 4 and 7 days after operation.RESULTSSeven days after operation, wound contracted obviously and most of the wounds connected well with the margin. In the control group, low dose group, medium dose group and high dose group, the wound healing rate were 7.67% +/- 5.46%, 29.01% +/- 7.43%, 26.54% +/- 11.49% and 10.39% +/- 3.96% respectively 2 days after operation; 28.16% +/- 13.76%, 37.99% +/- 13.05%, 42.00% +/- 9.56% and 39.58% +/- 12.74% respectively 4 days after operation; 59.08% +/- 19.02%, 64.15% +/- 17.92%, 77.39% +/- 8.45% and 69.78% +/- 8.45% respectively 7 days after operation. At 2 days after operation, significant differences were notified in healing rats between 3 sub-experimental groups and the control group (P < 0.05). Immunohistochemistry staining showed that there was a little more positive expression of laminin 5 2 days after operation that beneficial to promote the proliferation and differentiation of cell in every group, including positive cells and ECM. But in medium group there was fewer expression, only at the borderline and bottom of the wound, while the expression significantly increased 4 days after operation (P < 0.05) and there was a relative high expression 7 days after operation (P < 0.01).CONCLUSIONTbeta4 can inhibit the expression of laminin 5 early, and then up-regulate laminin 5 expression to moderate the reformation of ECM, promote the migration of epidemic cell and accelerate skin wound healing.