Post-inflammatory hyperpigmentation represents an acquired pigmentation anomaly frequently observed as a common sequela following acute or chronic skin inflammation, which often poses a challenge for treatment. We report a patient who developed persistent, mottled pigmentary macules all over her face subsequent to mesotherapy treatment. The patient was treated with a picosecond 1064 nm Nd:YAG laser in a two-step procedure way combined with a large- spot size, low-fluence mode and a fractional mode. After two treatment sessions, considerable improvement in her pigmentary lesions was observed, with no exacerbation or other complications.