Background: Hyperlipidemia, hyperlipoproteinemia, or dyslipidemia means the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood. Hyperlipoproteinemia happens when there are large amounts of lipids (fats) in the bloodstream. These lipids include triglycerides, phospholipids, cholesterol, and cholesterol esters. Aim of the work: this study aimed to evaluate the possible protective effect of Aphanizomenon flos-aquae (AFA) as a natural hypolipidemic product on body weight, hematological parameters, and FBG of adult male albino rats, in comparison with Slimquick (Orlistat 120 mg) as a synthetic hypolipidemic drug and their ability to treat hyperlipidemia or to prevent it. Material and methods: fifty-six male albino rats (Rattus albinus) were used and categorized into eight groups (7rats/group). The 1st group (C) rats were used as a control, the 2nd group (HFD) rats were treated  with high fat diet (HFD) (2% cholesterol)  to induce hyperlipidemia for 4 weeks only then scarified, the 3rd group (A) rats were orally administrated with AFA only for 4 weeks(94.5 mg/kg body weight /day), the 4th group (H+A1) rats were treated with HFD enriched with 2% cholesterol for 2 weeks to induce hyperlipidemia and the other 2 weeks were fed on the same HFD plus AFA extract administration, the 5th group (H+A2) rats were treated with HFD diet enriched with 2% cholesterol for 4 weeks to induce hyperlipidemia and then they were fed on normal basal diet (BD) plus AFA extract administration for another 2 weeks, the 6th group (S) rats were orally administrated with Slimquick only for 4 weeks (5 mg orlistat/rat/day), the 7th group (HFD+S1) rats  were treated with HFD diet enriched with 2% cholesterol for 2 weeks to induce hyperlipidemia and the other 2 weeks rats were fed on the same HFD plus Slimquick extract administration, the 8th group (HFD+S2) rats were treated with HFD diet enriched with 2% cholesterol for 4 weeks to induce hyperlipidemia and then they were fed on normal basal diet (BD) plus Slimquick extract administration for another 2 weeks. Results: Body weight, hematological parameters, and FBG changes were shown in the blood serum of rats, these changes included a very highly significant increase in the mean value of body weight gain, White blood cells count (W.B.C.s), and fasting blood glucose (FBS)in high-fat diet (HFD) group. In contrast, a significant decrease in Red blood cell count (R.B.C.s), Hemoglobin (HB) concentration, and hematocrit value (Hct%) in the high-fat diet group (HFD) was shown. Meanwhile, treatment with AFA or Slimquick ameliorated these results. Conclusion: Aphanizomenon flos-aquae extract as a natural product and Slimquick as a synthetic drug ameliorated the body weight, hematological parameters, and FBG changes in the blood serum of the high-fat diet (HFD) rats. Aphanizomenon flos-aquae extract proved to be a hypolipidemic agent better than Slimquick.