Abstract This article delves into the pentose phosphate pathway (PPP) in macrophages, highlighting its critical role in cellular metabolism and immune response. We explore the biochemical aspects of the pentose phosphate pathway, including its enzymatic reactions and metabolic intermediates, and how it is regulated in macrophages. The pentose phosphate pathway involvement in energy production, redox balance, and the synthesis of nucleotides and amino acids is examined, emphasizing its importance in macrophage function. We also discuss the pathway's implications in various diseases, including its dysregulation in metabolic disorders, neurodegenerative diseases, immune disorders, and cancer. The therapeutic potential of targeting the pentose phosphate pathway is explored, focusing on recent advances and future prospects for disease treatment. This comprehensive review underscores the pentose phosphate pathway significance in macrophage metabolism and its potential as a therapeutic target, offering insights into future research directions in this field.