Objective To analyze the effects of blood-glucose fluctuation on inflammatory hippocampus damage in diabetes mellitus model of rats. Methods The diabetic rats model (M) was established by injection of streptozotocin (STZ), the persistent high glucose diabetes rats model group (MS) was established by intraperitoneal injection of glucose, and the blood-glucose fluctuation rats model group (MF) was developed by alternative intraperitoneal injection of insulin and glucose administration. Body weight, glucose (Glu), triglyceride (TG), low density lipoprotein (LDL-C）and high density lipoprotein (HDL-C) were measured at 6 weeks after MF model establishment. The mRNA expression levels of IL-1β, IL-2, IL-6, IL-8 and TNF-α in the rat hippocampus were detected by real-time PCR. The influence of blood-glucose fluctuation on learning and memory function of hippocampus was observed using of Morris water maze. Results (1) The body weight of M group, MS group and MF group were significantly decreased comparing to normal rats group (N) (P<0.01). (2) 1 week after intravenous injection of STZ, the levels of Glu, TG and LDL-C in M group, MS group and MF group were significantly increased (all P<0.01), and HDL-C was significantly decreased comparing to N group (P<0.01). (3) Comparing to N group, the expression levels of IL-1β、IL-6、IL-8 and TNF-α mRNA in M, MS and MF groups were all changed significantly (all P< 0.05), while there was no significant difference in the expression of IL-2 mRNA in all rats groups (P> 0.05). The expression levels of IL-1β and TNF-α mRNA in MF group were significantly higher than those of M and MS group (all P<0.01). (4) The escape latency, the number of rats passing hidden platform and the swimming distance in the quadrant of hidden platform of M, MS and MF groups were significantly higher than those of N group (all P<0.01). And the escape latency, the number of rats passing hidden platform in MF group were significantly higher than those of M and MS groups. While there was no significant difference in swimming distance in the quadrant of hidden platform among M, MS and MF groups (P> 0.05). Conclusion Blood glucose fluctuation could induce inflammatory damage and dysfunction of hippocampus in rats more seriously than that induced by acute hyperglycemia and chronic persistent hyperglycemia.