Mechanical loading plays an essential role in both tendon development and degradation. However, the underlying mechanism of how tendons sense and response to mechanical loading remains largely unknown. SPARC, a multifunctional extracellular matrix glycoprotein, modulates cell extracellular matrix contact, cell-cell interaction, ECM deposition and cell migration. Adult mice with SPARC deficiency exhibited hypoplastic tendons in load-bearing zone. By investigating tendon maturation in different stages, we found that hypoplastic tendons developed at around postnatal 3 weeks when the mice became actively mobile. The in vitro experiments on primary tendon derived stem cells demonstrated that mechanical loading induced SPARC production and AKT/S6K signalling activation, which was disrupted by deleting SPARC causing reduced collagen type I production, suggesting that mechanical loading was harmful to tendon homeostasis without SPARC. In vivo treadmill training further confirmed that increased loading led to reduced Achilles tendon size and eventually caused tendon rupture in SPARC-/− mice, whereas no abnormality was seen in WT mice after training. We then investigate whether paralysing the hindlimb of SPARC-/− mice using BOTOX from postnatal 2 weeks to 5 weeks would delay the hypoplastic tendon development. Increased patellar tendon thickness was shown in SPARC-/− mice by reducing mechanical loading, whereas opposite effect was seen in WT mice. Finally, we identified a higher prevalence of a missense SNP in the SPARC gene in patients who suffered from a rotator cuff tear. In conclusion, SPARC is a mechano-sensor that regulates tendon development and homeostasis.