Objective To establish and characterize two chronic stress-related dry eye models—chronic unpredictable mild restraint (CUMR) and chronic unpredictable rhythm disturbance (CURD)—by comparing their phenotypic presentations, metabolomic profiles, and correlations with traditional Chinese medicine syndrome patterns. Methods: Thirty healthy male SPF rats were divided into the following groups: (1) Blank control group, (2) CUMR group, and (3) CURD group. The CUMR group underwent single-cage housing combined with behavioral restraint daily, while the CURD group received random rhythm intervention daily. After six weeks of modeling, general conditions, behavioral performance, and dry eye parameters were assessed. Histopathological alterations in the conjunctiva, cornea and lacrimal gland were examined via hematoxylin and eosin (HE) staining. Serum concentrations of 5-hydroxytryptamine (5-HT) and cortisol, alongside corneal levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were quantified using enzyme-linked immunosorbent assay (ELISA). Serum metabolomic profiling was conducted using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results: (1) Significant differences in appearance and behavior were observed between the CUMR and CURD groups. (2) Corneal fluorescein staining (CFS) significantly increased in the model groups, while tear volume and tear film breakup time (BUT) significantly decreased, with more pronounced changes in the CUMR group. (3) In the model group, no obvious inflammatory cell infiltration was observed in the cornea. The number of conjunctival goblet cells significantly decreased in the model groups, and the area of lacrimal gland vacuolation significantly increased. (4) ELISA results showed a significant decrease in serum 5-HT and a significant increase in cortisol, while no statistically significant differences were observed in corneal tissue TNF-α and IL-1β levels. (5) Serum metabolomic analysis revealed 235 differential metabolites identified in the CUMR and CURD groups, demonstrating a significant separation trend. Conclusion: Distinct stress modeling paradigms differentially impact host metabolism, culminating in divergent TCM syndrome manifestations and dry eye phenotypes. The CUMR model exemplifies a dry eye phenotype consistent with “Liver Depression and Spleen Deficiency”, potentially mediated by perturbations in tryptophan metabolism; conversely, the CURD model aligns with “Stagnation Heat in the Liver Channel”, likely arising from disruptions in the tricarboxylic acid cycle.