Background Multiple clinical trials have supported the idea that subcutaneously injected phosphatidylcholine (PPC) leads to a reduction in localized fat collection. However, only a few histological studies that explain the mechanism of action of PPC have been published. Aim This study aimed to evaluate the clinical and detailed histological changes in the skin and subcutaneous tissue after PPC injection. Patients and methods Ten female patients with local fat deposits (upper outer thigh) were assessed after a single session of subcutaneous injection with PPC on the basis of thigh circumference measurement, and histological examination of skin biopsy specimens was carried out before and 1 and 2 months after treatment. Histological sections were stained with H&E, Masson’s trichrome (for collagen fibers), and by aldehyde fuchsin (for elastic fibers), followed by morphometric study and statistical analysis. Results Two months after injection, a statistically significant reduction in thigh circumference was found (P=0.045), with leathery tight skin texture at the injected area. Histological examination revealed dermal inflammatory responses 1 month after injection, with destruction of fat cells. These observations were reduced after 2 months with evidence of regenerating fat cells. Statistical analysis showed a significant increase in collagen area% (P=0.025) and statistically nonsignificant increase in elastic fiber area% at the end of the study. Conclusion A single session of subcutaneous PPC injection had an evident lipolytic effect, with noticeable contouring and skin tightening due to regenerative effect on skin connective tissue, particularly dermal collagen. However, lipolytic effect was partially temporary because of regeneration of fat cells.