© 2014 Elsevier B.V. The present study was undertaken to evaluate the anti-dyslipidemic effects of nanoliposomes with different phospholipid compositions. Three sets of liposomal formulations (20. Mm; 100. nM in size) were prepared with low (SPC), medium (POPC) and high (HSPC) phase transition temperature values with and without cholesterol and anionic phosphatidyl glycerol (HSPC/DSPG; POPC/DMPG; SPC/EPG). The liposomal preparations were characterized for their size and zeta potential (dynamic light scattering), J774A.1 macrophages uptake (flow cytometry) and lipid-modifying effects (tyloxapol-induced hyperlipidemic mouse model). Anionic formulations displayed the highest rate of uptake by macrophages. Among them, HSPC/DSPG and SPC/EPG liposomes had the best lipid-modifying activity. These two formulations exerted favorable impact on all lipid profile parameters by reducing LDL-C (by up to 76% [HSPC/DSPG] and 86% [SPC/EPG]), total cholesterol (by up to 52% [HSPC/DSPG] and 68% [SPC/EPG]), triglycerides (by up to 88% [HSPC/DSPG] and 73% [SPC/EPG]), apoB (by up to 44% [HSPC/DSPG] and 35% [SPC/EPG]) and elevating HDL-C (by up to 85% [HSPC/DSPG] and 75% [SPC/EPG]) concentrations. Atherogenic indices were also effectively reduced following HSPC/DSPG (by up to 69%) and SPC/EPG (by up to 79%) injections. Empty, cholesterol-free nanoliposomal formulations containing 75% anionic phospholipid (PG) might serve as effective and rapid acting anti-dyslipidemic agents. Further research is warranted to confirm the observed anti-dyslipidemic effects of anionic nanoliposomes in diet-induced hyperlipidemic models, and also to evaluate the potential protective effects in regressing atheromatous lesions.