Objective To compare the refractive development and axial eye growth between Zmu-1:DHP and DHP guinea pig strains after weaning. Methods After screening of the refractive status of two strains of guinea pigs at 3 weeks of age, twelve Zmu-1:DHP guinea pigs and eight DHP guinea pigs were chosen. Each group underwent a series of ocular measurements at five time-points (4, 6, 8, 10 and 12 weeks), including refraction, axial length, corneal curvature and other ocular parameters. Results The refraction of 3-week old Zmu-1:DHP strain(n=327)was-5.19±3.92 D with a myopic rate of 85.1%. While the refraction of DHP strain guinea pigs (n=117) was 2.13±4.40 D with a myopic rate of 22.6%. From 4 to 12 weeks of age, the guinea pigs of Zmu-1:DHP strain developed toward more myopic, their anisometropia was larger than 1.5 D. The DHP strain had a stable refractive state. The Zmu-1:DHP guinea pig strain had larger axial length and vitreous thickness than strain DHP (t-test: P<0.01), and the DHP guinea pig strain had better vision (P<0.01). Astigmatism of Zmu-1:DHP strain guinea pigs changed significantly from 4 to 12 weeks (ANOVA: P<0.01), while DHP strain did not (ANOVA: P =0.07). In the Zmu-1:DHP strain, the refractive status had significant correlation with axial length (r=-0.785, P<0.01) and vitreous chamber depth (r=-0.754, P<0.01). In the DHP strain, the correlation coefficients were-0.19(P =0.089)and-0.34 (P<0.01). Conclusions Zmu-1:DHP strain guinea pigs have a higher rate of spontaneous myopia than DHP strain. The emmetropization is disrupted. This myopia is highly correlated with axial length and vitreous chamber depth.