The influence of sun exposure, gravity, and years of facial muscle movements starts to appear as wrinkles on the skin Hyaluronic acid injection can be used as a dermal filler to improve the skin's contour and reduce depressions in the skin. The present work aimed to examine the histopathological changes occurring in lower lip of the rats, as a result of HA injection and whether it could really bring us closer to the ̏ ideal soft tissue filler material ̋. To fulfill this aim, lip sections of rats treated with HA at various intervals were histologically examined using (H&E stain), in addition to histochemical examination using (Masson’s Trichrome & Toluidine Blue stain) and immunohistochemical analysis, using CD68 antibody. The study was conducted on thirty-six adult male rats with age ranging from 2 to 3 months and weight ranging from 150-200g. They were divided into two groups, each consisting of 18 rats, the first group represents the control group I and the second group represents the experimental group II. Each group was subdivided into three subgroups, according to the time of sacrifice with intervals of 7 days, 45 days and 90 days following injection as group I A, B and C and group II A, B and C respectively. In experimental group II, each rat received 0.07 ml of HA filler, which was injected into the lower lip, whereas group I served as positive control, where the animals were injected with 0.9 % saline into the lower rat's lip in the same way as those of experimental group.