Objective To investigate the relationship between gentamicin sulfate mediated gut microbi-ota in affecting glucolipid metabolism and inflammation with hypertension improvement.Methods Sprague-Dawley rats (8-weeks-old) were divided into the normal diet group (ND,n=11),high fat diet group (HFD,n=13) and HFD combined with gentamicin sulfate gavage group (GS,n=13).Blood pressure was monitored weekly during 5-13 weeks,and the levels of insulin,IL-1β,IL-6,TNF-α,LPS,TC,TG,LDL-C,HDL-C and homeostasis model assessment of insulin resistance index (HOMA-IR) were assessed at 13 weeks.The met-agenomic analyses were performed on DNA samples from rat colonic feces.Results The blood pressure in 13 weeks had no statistical difference among the three groups (P>0.05).The blood pressure during 5-10 weeks in the GS group was higher than that in the ND group with statistical difference (P<0.05).The blood pressure during 5-13 weeks in the HFD group was higher than that in the ND group,and the blood pressure during 10-13 weeks in the GS group was lower than that in the HFD with statistical difference (P<0.05). Compared with the group ND,the levels of TC,TG,LDL-C and HOMA-IR in the HFD group were higher,the HDL-C level was lower,and the differences were statistically significant (P<0.05).Compared with the HFD group,the levels of TG,LDL-C and HOMA-IR in the GS group were lower,the HDL-C level was higher,and the differences were statistically significant (P<0.05).The levels of LPS,IL-1β,IL-6 and TNF-α in the HFD group were higher than those in the ND group,while the GS group was lower than the HFD group (P<0.05).The partial least squares discriminant analysis showed that the intestinal microbiota in the HFD group and GS group was different in structure from that in the ND group.The family level results showed that the structure of the gut microbiota changed in three groups,including 24 microbiotas with significant changes.The hierarchical analysis showed that the proportion of f-desulphovibrio in the HFD group was higher than that in the ND group,while the GS group was lower the HFD group,and the differences were statistically significant (P<0.05).Conclusion Oral antibiotic gentamicin sulfate could improve the glucose and lipid metabolism ab-normalities and inflammation caused by HFD and its mechanism may be to relieve hypertension by regulating intestinal flora structure,abundance and LPS level.