Acid secretion containing sulfuric and hydrochloric acids is a fascinating defensive phenomenon within many groups of marine organisms. This study aimed to investigate the mice spleen histology and immunotoxicity using skin acid secretion (SAS) of the sea slug Berthellina citrina after oral administration. The spleen showed atrophy in the white pulp, decrease in the splenocytes density, megakaryocytes cytoplasmic degeneration as well as inflammatory cells infiltrations. The white and red pulp splenocytes number decreased time-dependently in the treated spleens. Additionally, the size of the megakaryocytes increased as compared with the control. The administration with SAS increased the number of the IgA+ cells aggregation in the splenic red pulp. Furthermore, after 7 days of the administration, large number of dispersed IgA+ cells were distributed in splenic parenchyma. The IgA+ cells numbers increased time dependently as compared with those in the control. The aggregation sizes and number of the F4/80+ cell in the splenic red pulp were increased. Furthermore the F4/80+ cells numbers increased time-dependently as compared with those in the control. The UEAI+ cells were found as free cells but not in aggregations in the control splenic red pulp. Contradictory to the number of IgA+ cells and F4/80+ cells the number of the UEAI+ cells decreased time-dependently after administration with SAS. Hematologically, abnormal numbers of WBCs different cells were observed after administration with SAS. This study provides new insight about the toxicity of a marine extract may be used in natural products industry or medical applications