Diabetes mellitus (DM) and hypothyroidism (HT) are prevalent diseases associated with dry eye (DE). Their impact on the lacrimal functional unit (LFU) is poorly known. This work evaluates the changes in the LFU in DM and HT. Adult male Wistar rats had the disease induced as follows: a) DM: Streptozotocin, b) HT: Methimazole. Tear film (TF) and blood osmolarity were measured. Cytokine mRNA was compared in the Lacrimal Gland (LG), trigeminal ganglion (TG), and cornea (CO). Oxidative enzymes were evaluated in the LG. DM had lower tear secretion (P=0.02) and higher blood osmolarity (P<0.001). DM presented lower mRNA expression of TRPV1 in the cornea (P=0.03), higher Il1b mRNA expression (P=0.03), and higher catalase activity in the LG (P<0.001). DM presented higher Il6 mRNA expression in the TG (P=0.02). The HT group had higher TF osmolarity (P<0.001), lower expression of Mmp9 mRNA in CO (P<0.001), higher catalase activity in the LG (P=0.002), and higher expression of Il1b mRNA in the TG (P=0.004). The findings revealed that DM and HT induce distinct compromises to the LG and the entire LFU.