The hematopoietic system is one of the potential targets of lead intoxication. Recognition of the lead-related deleterious outcomes promotes us to explore the potential therapeutic intervention. Here, we show that ginsenoside Rg1 (Rg1), extracted from the Chinese herb Panax ginseng, remarkably ameliorates the lead acetate-caused hematological index distortion as well as advanced hematopoietic stem cells (HSCs) aging and aging associated inflammation response. Specifically, Rg1 administration alleviated the increment of aging associated p53-p21-Rb signaling in aged HSCs induced by lead acetate. It also led a reduction of the lead acetate-induced increased inflammation level in blood plasma, which also partly contribute the aged HSCs rejuvenation. In conclusion, our results indicate that ginsenoside Rg1 therapeutically alleviated the essential blood deficits and advanced HSCs aging by lead acetate exposure, by which it could be viewed as a potential candidate for lead acetate-caused blood toxicity treatment.