Purpose Ephedrine has various side effects in the cardiovascular and nervous systems. However, the cellular mechanism of toxicity remains unknown, specifically on the retina. This study was to investigate effects of ephedrine on the retina and explore the underlying mechanisms. Methods Sprague Dawley rats were treated with ephedrine (n = 10) or saline (n = 10) by oral gavage for seven days. The retinal morphology was evaluated by Toluidine blue staining. Apoptosis-related markers were detected in the retinal lysate. Enzyme-linked immunosorbent assays were used to measure neurotransmitters and oxidative stress markers. Real-time PCR and western blot were used to measure gene and protein expression, respectively. Results Our results demonstrated that ephedrine induced apoptosis in the retina, increased dopamine level as well as oxidative stress, and down-regulated theJak2/Stat3gene expression as well as protein expression of p-JAK2/p-STAT3. Conclusions Our study indicated that ephedrine treatment caused retinal damage in SD rats, which may be associated with the JAK2/STAT3 pathway.