AIM: To observe changes in the flash electroretinogram(ERG)and retinal microcirculation in mice suspended by their tails, an animal model that simulates cephalad movement of bodily fluids under conditions of microgravity.METHODS: Thirty-six adult male C57BL/6J mice(36 eyes)were randomly divided into three experimental groups and three control groups. Mice in the experimental groups were tail-suspended for 15d(Group one), tail-suspended for 30d(Group two), or tail-suspended followed by returning to normal position for 30d(Group three). Three control groups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15, 30, and 60d. The mice were immediately examined using scotopic ERG(including oscillatory potentials \〖OPs\〗)and fundus fluorescein angiography(FFA)in vivo, and subsequently sacrificed to analyze the retinal histology(methods including immunohistochemistry and TUNEL staining)in vitro. Independent sample t-test was used for data comparison between the same time-point groups.RESULTS: Following 15-days' tail-suspension, scotopic ERG showed a decline in OPs, but not in the b-wave; the second OP(O2)showed an amplitude of 197±33μV, which was about 60% of the control level(t=-5.938, P2 showing an average value of 264±39μV; when compared to the corresponding control group(308±41μV), no significant difference was observed(t=-1.887, P>0.05). Morphologically, only the 15-days' tail-suspended mice showed FFA with microvascular dilation and tortuosity. Rhodopsin and cone-opsin were almost normal and no apoptotic-positive signals were detected in the retinas of the three tail-suspended groups.CONCLUSION: Simulating cephalad shifting of bodily fluids as under microgravity, using short-term tail-suspension can affect rodent ERG and retinal microcirculation; however, the change is reversible with no obvious permanent injury observed in the retinas.