Meaning
To leave quickly / run away
Example
Quando a polícia chegou, todo mundo picou a mula.
When the police arrived, everyone ran away quickly.
Origin
From mule riding: picar ("to spur/prod") the mule to make it gallop. The image of spurring a mount to leave in a hurry survives in colloquial Brazilian Portuguese as a vivid way to say "get out of here fast".
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More idioms
Acertar na moscaTo guess correctly / To hit the nail on the headAmigo da onçaA fake/false friendAndar na linhaTo toe the line / To behave properlyArmar um barracoTo cause a public sceneRodar a baianaTo cause a public scene / To go ballisticArrumar sarna pra se coçarTo ask for troubleArrastar as asasTo hit on someone / To flirtAbrir o jogoTo come clean / To open upArregaçar as mangasTo roll up one's sleeves / To get to workAgarrar com unhas e dentesTo hold on for dear life / To seize an opportunity