AIM: To evaluate the effect of different monochromatic lights on the refractive status and the secretion levels of neurotransmitters in the progressive myopic model of guinea pigs. METHODS: Guinea pigs (n=90) underwent different monochromatic lights irradiation for two weeks were randomly divided into 6 groups: white light (control), ultraviolet (UV), blue, green, red, and simulative sunlight (simSUN). The refractive status and axial length (AL) were measured. Transmission electron microscopy, Masson’s trichrome staining and hematoxylin-eosin staining were performed to observe the structural changes of retina and sclera. High-performance liquid chromatography (HPLC), western blotting and immunofluorescence were used to measure neurotransmitters and their receptors. RESULTS: Myopia models were established successfully. When compared the degrees of change in myopic eyes of control group, the UV group showed a minor decrease in AL and refraction, along with a significant increase in scleral thickness. In contrast, the red and green groups revealed a net increase in AL and refraction, coupled with a net decrease in scleral thickness (all, P<0.01). The dopamine concentration increased in the UV group, while concentrations of serotonin and melatonin significantly decreased (all, P<0.01). The groups that were exposed to UV, blue and simSUN, the expression of dopamine receptor D2 (DRD2) increased, and the expression of hydroxytryptamine receptor 2A (HTR2A) and melatonin receptor type 2 (MT2) decreased significantly when compared to the control group (all P<0.01). CONCLUSION: Exposure to short-wavelength light could slow the development of myopia by promoting the production of dopamine and suppressing the serotonin and melatonin concentration. The neurotransmitter receptors MT2, DRD2, and HTR2A in the sclera appear to play different roles by different color lights in myopic guinea pigs.