Aim To investigate the efficacy and safety of long-term oral rosuvastatin combined with metformin in patients with hyperlipidemia. Methods 522 patients with hyperlipidemia were randomly divided into combined medication group (262 cases) and control group (260 cases). The combined medication group was given rosuvastatin calcium 10 mg combined with metformin, and the control group was given rosuvastatin calcium 20 mg. Follow-up for 24 months, compared the two groups of blood lipid levels, new diabetes mellitus incidence, impaired glucose tolerance incidence, the incidence of hypoglycemia symptoms, and impact on liver enzymes, muscle enzymes, renal function. Results The serum high density lipoprotein cholesterol (HDLC) in the combined medication group was higher than that in control group, and the serum triglyceride (TG) level was lower than that of control group (P<0.05). The incidence of new diabetes mellitus and impaired glucose tolerance were lower in combined medication group than that in control group, but gastrointestinal reaction was higher (P<0.01). Other indexes had no significant difference(P>0.05). Conclusion Compared with the large dosage of statin for a long time, the small dosage of statin combined with metformin is more safe and effective.