Aloe vera is a widely used natural herb from which many sorts of commercial products have been derived using different preparation technologies. Aloe whole-leaf powder is one of the most popular subtypes. The long-term impact of aloe products has already been reported; however, there have been few studies about short-term exposure, and especially about the relative impact of Aloe vera whole-leaf freeze-dried powder (AWFP). To provide more toxicological data and to document the early changes induced by AWFP, in this study 120 SD rats were divided into four groups (control and 400/1200/2000 mg/kg treatment groups) and were administered AWFP once daily by oral gavage for 28 consecutive days, followed by a two week recovery phase. The results showed that AWFP could induce soft/loose changes in faeces. Significantly decreased white blood cell (WBC) counts, associated with reduced lymphocyte counts were also noted. The relative organ weight, including both organ-to-body weight ratio and organ-to-brain weight ratio of kidneys, was significantly increased in 2000 mg/kg compared with that in controls. Histopathologically, pigmentation in the kidneys and increased mucosal thickness in colon were also noted in a dose response groups. Other changes observed in the study were not considered to be treatment related, and 400 mg/kg was considered as the no-observed-adverse-effect level. The study provided clear evidence of treatment-related changes with a short-term exposure to AWFP. This is also the first report of the early colon morphologic changes associated with stool changes noted previously in-life phase, providing additional toxicity data which will contribute to our understanding about the short-term usage of AWFP as a remedy.