Tissue expansion is a helpful technique in reconstructive plastic surgery. Unfortunately, tissue expansion still needs to be improved. Twenty-four male Wistar rats were used to evaluate the effect of estriol on tissue expansion. The agents hyaluronidase, estriol, and base cream (as a control) were applied topically to separate animal groups for 5 weeks, and their effects were studied on tissue expansion. Both hyaluronidase (p < 0.05) and estriol (p < 0.001) enhanced the rate of expansion when compared with control animals. Estriol was more effective than hyaluronidase (p < 0.05). Breaking strengths were measured in the estriol and the control groups. Breaking strength was not evaluated in the hyaluronidase group because of the necrotic changes seen at the end of the fifth week. The breaking strength was higher in the control group than in the estriol group (p < 0.05). The authors suggest that topical estriol be used as an adjunctive agent to facilitate tissue expansion.