Purpose: To determine whether hepatocyte growth factor (HGF) and insulin-like growth factor-I (IGF-I) have synergistic effects in promoting extraocular muscle fiber growth and force generation. Methods: A superior rectus muscle of adult rabbits was treated with either a single injection of HGF or sequential injections of HGF followed 1 week later by IGF-I. One week after HGF alone and 1 week after the IGF-I injection, the superior rectus muscles from treated and control orbits were examined for alterations in force generation as well as changes in myofiber size. Results: Injection of HGF alone did not result in changes to muscle force, specific tension, or myofiber cross-sectional area; however, it did result in a significant increase in numbers of satellite cells. Sequential injection of HGF and IGF-I resulted in significantly increased force, specific tension, and myofiber cross-sectional areas as well as increased numbers of satellite cells. Conclusions: Preinjection with HGF augments the treatment effect of IGF-I. This synergistic effect is likely a result of HGF-induced activation of satellite cells and should allow a reduction in IGF-I dosing required to produce a given increase in extraocular muscle force generation.