Biofertilizer production and application for sustainable agriculture is already a reality. The methods for biofertilizers delivery in crop fields are diverse. Although foliar spray is gaining wide acceptance, little is known about the influence that the biochemical features of leaves have on the microbial colonization. Arthrobacter agilis UMCV2 is a rhizospheric and endophytic bacteria that promotes plant growth and health. In this study, we determined the capacity of the UMCV2 strain to colonize different leaves from Medicago truncatula in a foliar inoculation system. By using two powerful analytical methods based on mass spectrometry, we determined the chemical profile of the leaves in 15-d old plants. The metabolic signatures between the unifoliate leaf (m1) and the metameric units developing above (m2 and m3) were different, and interestingly, the highest colony forming units (CFU) was found in m1. The occurrence of the endophyte strongly affects the sugar composition in m1 and m2 leaves. Our results suggest that A. agilis UMCV2 colonize the leaves under a foliar inoculation system independently of the phenological age of the leaf and it is capable of modulating the carbohydrate metabolism without affecting the rest of the metabolome. Plants live in a close relationship with different microbial communities that reside inside or outside the plant tissues. The inside colonizers are referred as endophytes (from the Greek endon-within and phyton-plant), and when they are inside the plant, they completely depend on the plant and its internal conditions for growth 1-5. A study of Arabidopsis thaliana grown under natural conditions showed that the bacterial community associated with the outside of the roots were more diverse than in the endophytic community, while the opposite pattern was observed in the leaves 6. In addition, the authors found that leaves and roots shared many species of bacterial endophytes, suggesting that some root endosphere colonizers migrate and are capable of colonizing above-ground tissues; thus the microbial traits for competition and colonization influence the richness and composition of the plant endophytes 7,8. According to the literature, the endophytes are non-pathogenic, but some of them could act as latent pathogens that can cause disease, depending on the stressful environmental circumstances 4,9. Studies of the functional capacity of beneficial endophytes have revealed their potential as promoters of plant growth and health, moreover, they are free from the environmental pressure of changing soil and climate conditions experienced by their rhizospheric counterparts, so they are an excellent candidate for biofertilizers 10,11. The delivery methods of endophytes in agriculture include seed inoculation, soil drenching, stem injection, and foliar fertilization. Currently, there is a renewed interest in a foliar-treated plants and different studies on the effect of bacterial and fungal endophytes on the growth, crop production, nutrient uptake, and defense have appeared in the literatu...